CORRESPONDENCE: LETTER TO THE EDITOR
Risk Associated With Statin Treatment
John Kjekshus, MD, PhD*
* Department of Cardiology, Rikshospitalet University Clinic, University of Oslo, Sognsvannsveien 20, 0027 Oslo, Norway (Email: john.kjekshus{at}medicin.uio.no).
Several prospective, randomized, placebo-controlled trials have established the fundamental preventive role of statins in the treatment of atherosclerotic disease, including coronary artery disease, stroke, and peripheral artery disease. However, in high-risk cohorts of elderly, hypertensive patients and patients with heart failure, low cholesterol portends a poor prognosis (1,2). This controversial association has been ascribed to the role of cholesterol as a marker of incipient risk, which disappears after accounting for the early deaths (3). In their retrospective meta-analysis of statin users in large randomized, controlled trials, Alsheikh-Ali et al. (4) observed an association between statin-induced lowering of low-density lipoprotein and increased risk of cancer, and they concluded that this may offset some of the benefits of statins. Their conclusion of a relationship is most likely spurious and dependent on an association between incipient cancer risk and attainment of low levels of low-density lipoprotein. Unfortunately, they only reported on the statin groups. It would have been helpful if they excluded a similar association among the placebo groups and if they had presented data excluding deaths within the first year after onset of statin treatment, which may be confounders. In the longest follow-up of any statin trial, 4S (Scandinavian Simvastatin Survival Study) demonstrated that after 10 years there was a nonsignificant trend toward less cancer among patients who received simvastatin treatment during the trial period (5).
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References
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- Horwich TB, Hamilton MA, Maclellan WR, Fonarow GC. Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure J Card Fail 2002;8:216-224.[CrossRef][ISI][Medline]
- Rauchhaus M, Clark AL, Doehner W, et al. The relationship between cholesterol and survival in patients with chronic heart failure J Am Coll Cardiol 2003;43:1933-1940.
- Corti M-C, Guralnik JM, Salive ME, et al. Clarifying the direct relation between total cholesterol levels and death from coronary heart disease in older persons Ann Intern Med 1997;126:153-160.
- Alsheikh-Ali AA, Maddukuri PV, Han H, Karas RH. Effect of the magnitude of lipid lowering on risk of elevated liver enzymes, rhabdomyolysis, and cancer J Am Coll Cardiol 2007;50:409-418.[Abstract/Free Full Text]
- Strandberg TE, Pyörälä K, Cook TJ, et al. Mortality and incidence of cancer during 10-year follow-up of the Scandinavian Simvastatin Survival Study Lancet 2004;364:771-777.[CrossRef][ISI][Medline]
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- Alawi A. Alsheikh-Ali and Richard H. Karas
J. Am. Coll. Cardiol. 2008 51: 92.
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